4tr8 | pdb_00004tr8
Crystal structure of DNA polymerase sliding clamp from Pseudomonas aeruginosa
Structural highlights
FunctionDPO3B_PSEAE Confers DNA tethering and processivity to DNA polymerases and other proteins. Acts as a clamp, forming a ring around DNA (a reaction catalyzed by the clamp-loading complex) which diffuses in an ATP-independent manner freely and bidirectionally along dsDNA. Initially characterized for its ability to contact the catalytic subunit of DNA polymerase III (Pol III), a complex, multichain enzyme responsible for most of the replicative synthesis in bacteria; Pol III exhibits 3'-5' exonuclease proofreading activity. The beta chain is required for initiation of replication as well as for processivity of DNA replication.[UniProtKB:P0A988] Publication Abstract from PubMedBacterial sliding clamps are molecular hubs that interact with many proteins involved in DNA metabolism through their binding, via a conserved peptidic sequence, into a universally conserved pocket. This interacting pocket is acknowledged as a potential molecular target for the development of new antibiotics. We previously designed short peptides with an improved affinity for the Escherichia coli binding pocket. Here we show that these peptides differentially interact with other bacterial clamps, despite the fact that all pockets are structurally similar. Thermodynamic and modeling analyses of the interactions differentiate between two categories of clamps: group I clamps interacts efficiently with our designed peptides and assembles the Escherichia coli and related orthologs clamps, while group II poorly interact with the same peptides and includes Bacillus subtilis and other Gram+ clamps. These studies also suggest that the peptide binding process could occur via different mechanisms depending on which type of clamp it binds to. Differential Modes of Peptide Binding onto Replicative Sliding Clamps from Various Bacterial Origins.,Wolff P, Amal I, Olieric V, Chaloin O, Gygli G, Ennifar E, Lorber B, Guichard G, Wagner JE, Dejaegere A, Burnouf DY J Med Chem. 2014 Aug 29. PMID:25170813[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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